Des-γ-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma

Mayumi Suzuki, Hidenori Shiraha, Tatsuya Fujikawa, Nobuyuki Takaoka, Naoki Ueda, Yutaka Nakanishi, Kazuko Koike, Akinobu Takaki, Yasushi Shiratori

Research output: Contribution to journalArticle

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Abstract

Des-γ-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with cell surface receptor Met causing Met autophosphorylation and also to activate STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis showed that DCP induced STAT3-related transcription. Small interfering RNAs against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1-STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell proliferation.

Original languageEnglish
Pages (from-to)6409-6415
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number8
DOIs
Publication statusPublished - Feb 25 2005

Fingerprint

Prothrombin
Hepatocellular Carcinoma
Intercellular Signaling Peptides and Proteins
Janus Kinase 1
Cell proliferation
Cells
Cell Proliferation
Cell Line
1-Phosphatidylinositol 4-Kinase
Cell Surface Receptors
Transcription
Tumor Biomarkers
Phosphatidylinositols
Mitogen-Activated Protein Kinases
Luciferases
Reporter Genes
Mitogens
Small Interfering RNA
Phosphotransferases
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Des-γ-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma. / Suzuki, Mayumi; Shiraha, Hidenori; Fujikawa, Tatsuya; Takaoka, Nobuyuki; Ueda, Naoki; Nakanishi, Yutaka; Koike, Kazuko; Takaki, Akinobu; Shiratori, Yasushi.

In: Journal of Biological Chemistry, Vol. 280, No. 8, 25.02.2005, p. 6409-6415.

Research output: Contribution to journalArticle

Suzuki, M, Shiraha, H, Fujikawa, T, Takaoka, N, Ueda, N, Nakanishi, Y, Koike, K, Takaki, A & Shiratori, Y 2005, 'Des-γ-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma', Journal of Biological Chemistry, vol. 280, no. 8, pp. 6409-6415. https://doi.org/10.1074/jbc.M406714200
Suzuki, Mayumi ; Shiraha, Hidenori ; Fujikawa, Tatsuya ; Takaoka, Nobuyuki ; Ueda, Naoki ; Nakanishi, Yutaka ; Koike, Kazuko ; Takaki, Akinobu ; Shiratori, Yasushi. / Des-γ-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 8. pp. 6409-6415.
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AU - Ueda, Naoki

AU - Nakanishi, Yutaka

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